Calbindin
Encyclopedia
Calbindin refers to several calcium
-binding proteins. They were originally described as vitamin D-dependent calcium-binding protein
s in the intestine and kidney in the chick and mammals. They are now classified in different sub-families as they differ in the number of Ca2+ binding EF-hand sites.
. It is encoded in humans by the CALB1 gene.
Calbindin-D28k contains 4 active calcium-binding domain
s, and 2 modified domains that have lost their calcium-binding capacity. Calbindin-D28k acts as a calcium buffer and calcium sensor and can hold four Ca2+ in the EF-hands of loops EF1, EF3, EF4 and EF5. The structure was solved using high-resolution NMR and which was one of the largest proteins then to be determined. The sequence of Calbindin is 263 residues in length and has only one chain. The sequence consists mostly of alpha helicies but beta sheets are not absent. According to the PDB it is 44% helical with 14 helices containing 117 residues, and 4% beta sheet with 9 strands containing 13 residues.
Calbindin-D28k is a vitamin D
responsive gene in many tissues, in particular the chick intestine, where it has a clear function in mediating calcium absorption. In the brain, its synthesis is independent of vitamin-D.
There is no homology
between calbindin-D28k and calbindin-D9k, apart from their calcium binding domains (EF-hands): calbindin-D9k has two EF-hands, and calbindin-D28k has six.
ian intestinal epithelial cells (enterocytes). Calbindin-D9k can also be found in the kidney and uterus
in some mammalian species. It in encoded in humans by the S100G
gene which has also been termed CALB3.
Calbindin-D9k is a member of the S100
family of calcium-binding proteins. It has two EF-hands sequences which bind Ca2+ with high affinity.
Calbindin-D9k mediates the transport of calcium across the enterocytes from the apical side, where entry is regulated by the calcium channel
TRPV6
, to the basolateral side, where calcium pump
s such as PMCA1 utilize intracellular adenosine triphosphate
to pump calcium into the blood. The transport of calcium across the enterocyte cytoplasm appears to be rate-limiting for calcium absorption in the intestine; the presence of calbindin increases the amount of calcium crossing the cell without raising the free concentration. Calbindin-D9k may also stimulate the basolateral calcium-pumping ATPase
s. Expression
of calbindin-D9k, like that of calbindin-D28k, is stimulated by the active vitamin D metabolite
, calcitriol
although the precise mechanisms are still controversial. In mice in which the receptor for vitamin D is not expressed
, calbindin-D9k is reduced, but not absent.
Calcium in biology
Calcium plays a pivotal role in the physiology and biochemistry of organisms and the cell. It plays an important role in signal transduction pathways, where it acts as a second messenger, in neurotransmitter release from neurons, contraction of all muscle cell types, and fertilization...
-binding proteins. They were originally described as vitamin D-dependent calcium-binding protein
Vitamin D-dependent calcium-binding protein
Vitamin D-dependent calcium binding proteins were discovered in the cytosolic fractions of chicken intestine, and later in mammalian intestine and kidney, by workers including Robert Wasserman of Cornell University....
s in the intestine and kidney in the chick and mammals. They are now classified in different sub-families as they differ in the number of Ca2+ binding EF-hand sites.
Calbindin-D28k
Calbindin-D28k was first shown to be present in the intestine in birds and then found in the mammalian kidney. It is also expressed in a number of neuroendocrine cells, particularly in the cerebellumCerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
. It is encoded in humans by the CALB1 gene.
Calbindin-D28k contains 4 active calcium-binding domain
Protein domain
A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
s, and 2 modified domains that have lost their calcium-binding capacity. Calbindin-D28k acts as a calcium buffer and calcium sensor and can hold four Ca2+ in the EF-hands of loops EF1, EF3, EF4 and EF5. The structure was solved using high-resolution NMR and which was one of the largest proteins then to be determined. The sequence of Calbindin is 263 residues in length and has only one chain. The sequence consists mostly of alpha helicies but beta sheets are not absent. According to the PDB it is 44% helical with 14 helices containing 117 residues, and 4% beta sheet with 9 strands containing 13 residues.
Calbindin-D28k is a vitamin D
Vitamin D
Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....
responsive gene in many tissues, in particular the chick intestine, where it has a clear function in mediating calcium absorption. In the brain, its synthesis is independent of vitamin-D.
There is no homology
Homology (biology)
Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...
between calbindin-D28k and calbindin-D9k, apart from their calcium binding domains (EF-hands): calbindin-D9k has two EF-hands, and calbindin-D28k has six.
Calretinin
Calretinin is a 29kDa protein with 58% homology to calbindin-D28k and principally found in nervous tissues. It is encoded in humans by the CALB2 gene.Calbindin-D9k
Calbindin-D9k is present in mammalMammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
ian intestinal epithelial cells (enterocytes). Calbindin-D9k can also be found in the kidney and uterus
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...
in some mammalian species. It in encoded in humans by the S100G
S100G
Protein S100-G is a protein that in humans is encoded by the S100G gene.-Further reading:...
gene which has also been termed CALB3.
Calbindin-D9k is a member of the S100
S100
S100 or S-100 can refer to:* S-100 bus, a type of computer bus* S-100 protein, a family of cellular antigens proteins* Hondata s100, a engine tuning system for Honda and Acura cars* QTEK S100, a re-badged HTC Magician Pocket PC phone...
family of calcium-binding proteins. It has two EF-hands sequences which bind Ca2+ with high affinity.
Calbindin-D9k mediates the transport of calcium across the enterocytes from the apical side, where entry is regulated by the calcium channel
Calcium channel
A Calcium channel is an ion channel which displays selective permeability to calcium ions. It is sometimes synonymous as voltage-dependent calcium channel, although there are also ligand-gated calcium channels.-Comparison tables:...
TRPV6
TRPV6
TRPV6 is a membrane calcium channel which is responsible for the first step in calcium absorption in the intestine. It was first named CAT1, or ECaC2, and has been described in the intestine in several species, including humans. It is located in the apical brush-border membrane of the intestinal...
, to the basolateral side, where calcium pump
Calcium pump
There is a very large transmembrane electrochemical gradient of Ca2+ driving the entry of the ion into cells, yet it is very important for cells to maintain low concentrations of Ca2+ for proper cell signalling; thus it is necessary for the cell to employ ion pumps to remove the Ca2+.The PMCA and...
s such as PMCA1 utilize intracellular adenosine triphosphate
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
to pump calcium into the blood. The transport of calcium across the enterocyte cytoplasm appears to be rate-limiting for calcium absorption in the intestine; the presence of calbindin increases the amount of calcium crossing the cell without raising the free concentration. Calbindin-D9k may also stimulate the basolateral calcium-pumping ATPase
ATPase
ATPases are a class of enzymes that catalyze the decomposition of adenosine triphosphate into adenosine diphosphate and a free phosphate ion. This dephosphorylation reaction releases energy, which the enzyme harnesses to drive other chemical reactions that would not otherwise occur...
s. Expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
of calbindin-D9k, like that of calbindin-D28k, is stimulated by the active vitamin D metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...
, calcitriol
Calcitriol
Calcitriol , also called 1,25-dihydroxycholecalciferol or 1,25-dihydroxyvitamin D3, is the hormonally active form of vitamin D with three hydroxyl groups...
although the precise mechanisms are still controversial. In mice in which the receptor for vitamin D is not expressed
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
, calbindin-D9k is reduced, but not absent.